Virtual and experimental screening of phenylfuranchalcones as potential anti-Leishmania candidates

Discovery of novel or repurposed chemical treatments for leishmaniasis is a priority given the limited number of therapeutic alternatives available. One way to accelerate the finding is by implementing virtual screening methodologies using structural information, with subsequent experimental validations. Here we tested a library of 48 phenylfuranchalcones as anti-Leishmania agents that can be associated to the potential inhibition of a protein target within the parasite. For that purpose, a list of 43 protein structures from different Leishmania species was prepared to dock the virtual compound library. The protein with the best predicted scores was used as reference to select a subset of previously synthesized compounds for in vitro validation of their cytotoxicity and anti-Leishmania activity. We found a set of active compounds (EC₅₀ < 25 μM) that were compared with the computational results using Spearman correlations. The analysis allowed us to propose the inhibition of a phosphodiesterase enzyme as the potential mechanism of action.